Little evidence for an effect of smoking on multiple sclerosis risk: A Mendelian Randomization study

Abstract

The causes of multiple sclerosis (MS) remain unknown. Smoking has been associated with MS in observational studies and is often thought of as an environmental risk factor. We used two-sample mendelian randomization (MR) to examine whether this association is causal using genetic variants identified in genome-wide association studies (GWASs) as associated with smoking. We assessed both smoking initiation and lifetime smoking behaviour (which captures smoking duration, heaviness, and cessation). There was very limited evidence for a meaningful effect of smoking on MS susceptibility as measured using summary statistics from the International Multiple Sclerosis Genetics Consortium (IMSGC) meta-analysis, including 14,802 cases and 26,703 controls. There was no clear evidence for an effect of smoking on the risk of developing MS (smoking initiation: odds ratio [OR] 1.03, 95% confidence interval [CI] 0.92–1.61; lifetime smoking: OR 1.10, 95% CI 0.87–1.40). These findings suggest that smoking does not have a detrimental consequence on MS susceptibility. Further work is needed to determine the causal effect of smoking on MS progression.

Assessment of the genetic and clinical determinants of hip fracture risk: Genome-wide association and Mendelian randomization study

“…For ever smoked regularly, the ORs are expressed per 0.5 unit increase in log odds of ever smoking regularly with a 1 standard deviation increase in genetically predicted smoking initiation corresponding to a 10% increased risk of smoking. 18 , 22 Estimates are displayed using a random effects model to account for possible heterogeneity. ∗, the ORs differ significantly between hip fracture and fractures at any bone site as determined by a z test.…”

Neuroinflammation in neurodegeneration via microbial infections

“…Several studies have recognized that cigarette smoking might be a risk factor for NDs, including MS ( 33 ), AD ( 34 , 35 ), and PD ( 36 ), thereby suggesting a new pathway known as the ‘lung-brain axis’. Like other organs, the lungs also have a microbial community that are known as pulmonary microbes, which can directly impact the lung health and development of diseases, and indirectly be detrimental to other organs, including the brain ( 37 ).…”

A systematic review of Mendelian randomization studies on multiple sclerosis

“…In supporting observational epidemiological studies suggesting the deleterious effect of smoking on MS risk (Degelman & Herman, 2017), Mitchell et al (2020) investigated the causal effect of smoke on MS risk. The not statistically significant IVW estimates revealed lack of evidence for a causal effect of either smoking initiation, a measure indicating whether an individual had ever smoked regularly, or lifetime smoking, a measure indicating smoking initiation, duration, heaviness and cessation, on MS risk.…”